Author:
Silva-Pavez Eduardo,Mendoza Elizabeth,Morgado-Cáceres Pablo,Ahumada-Castro Ulises,Bustos Galdo,Kangme-Encalada Matías,de Arbina Amaia Lopez,Puebla-Huerta Andrea,Muñoz Felipe,Cereceda Lucas,Varas-Godoy Manuel,Hidalgo Yessia,Cardenas J. Cesar
Abstract
AbstractIncreasing evidence supports the hypothesis that cancer progression is under mitochondrial control. Mitochondrial fission plays a pivotal role in the maintenance of cancer cell homeostasis. The inhibition of DRP1, the main regulator of mitochondrial fission, with the mitochondrial division inhibitor (mdivi-1) had been associated with cancer cell sensitivity to chemotherapeutics and decrease proliferation. Here, using breast cancer cells we find that mdivi-1 induces the detachment of the cells, leading to a bulk of floating cells that conserved their viability. Despite a decrease in their proliferative and clonogenic capabilities, these floating cells maintain the capacity to re-adhere upon re-seeding and retain their migratory and invasive potential. Interestingly, the cell detachment induced by mdivi-1 is independent of DRP1 but relies on inhibition of mitochondrial complex I. Furthermore, mdivi-1 induces cell detachment rely on glucose and the pentose phosphate pathway. Our data evidence a novel DRP1-independent effect of mdivi-1 in the attachment of cancer cells. The generation of floating viable cells restricts the use of mdivi-1 as a therapeutic agent and demonstrates that mdivi-1 effect on cancer cells are more complex than anticipated.
Funder
Fondo Nacional de Desarrollo Científico y Tecnológico
Fondo de Financiamiento de Centros de Investigación en Áreas Prioritarias
Publisher
Springer Science and Business Media LLC